Recent data has suggested that latent adenoviral infections may up-regulate inflammatory processes in the lung and be an important co-factor in emphysema development. In addition recent lung biopsy studies have demonstrated that lung lymphocytes, particularly CD8+ cells are found more commonly in the airway as well as the lung parenchyma in individuals with chronic obstructive pulmonary disease. It has thus been hypothesized that lymphocytes associated with chronic obstructive pulmonary disease represent a cytotoxic T-lymphocyte (CTL) response to latent virus. In support of this hypothesis is data demonstrating a marked increased susceptibility of HIV infected smokers to emphysema. Furthermore, the presence of emphysema in this precocious process is associated with increased numbers of cytotoxic lymphocytes on broncho- alveolar lavage. With this as a background, the central hypothesis of the present study is that CTL's represent a response to latent viral infection in the lung and contribute directly to emphysema pathogenesis by accelerating apoptotic cell death of lung parenchyma. To address this hypothesis, we examine use lung tissue obtained from subjects enrolled in the National Emphysema Treatment Trial undergoing lung volume reduction surgery (LVRS). The specific aims of the current proposal are: Specific Aim 1: To determine the relationship between latent virus infection of lung epithelium, CTL infiltration and programmed cell death in patients with advanced emphysema. Specific Aim 2: To determine whether latent viral infection of alveolar epithelium predicts progression of emphysema following LVRS. In conclusion, we believe that successful completion of this project will provide us with very important information regarding the role of latent viral infection, upregulation of the inflammatory response and the pathogenesis of emphysema.